| Project/Area Number |
12670540
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MIYAMOTO Kenji Hokkaido Univ., College of Medical Technology, Prof., 医療技術短期大学部, 教授 (50190814)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIHIRA Jun Hokkaido Univ., Grad. School of Med., Asso. Prof., 大学院・医学研究科, 助教授 (30189302)
NISHIMURA Masaharu Hokkaido Univ., Grad. School of Med., Prof., 大学院・医学研究科, 教授 (00208224)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | MIF / LUNG INJURY / lipopolysaccharide / Transgenic mice / NEUTROPHIL / ARDS / GLUCOCORTICOIDS / 肺障害 |
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| Research Abstract |
Macrophage migration inhibitory factor (MIF) is a unique cytokine, a hormone, or an enzyme, which reportedly overrides the anti-inflammatory effect of endogenous glucocorticoides. We demonstrated that anti-MIF antibody attenuated lipopolysaccharide (LPS)-induced neutrophil accumulation in rats lungs, at least in part, via suppressing the level of neutrophil chemokine macrophage inflammatory protein-2.
To clarify the further mechanism of MIF in the lung injury, we tested the effect of anti-MIF antibody in the other types of lung injury. We also examined the effect of IPS on the lung injury in MIF transgenic mice.
1. Role of MIF in bleomycin-induced lung injury and fibrosis.
We measured the levels of MIF in lung tissues and brochoalveolar lavage (BAL) at certain time points after intratracheal administration of BLM, and examined whether anti-MIF antibody attenuates BIM-induced acute lung injury and subsequent fibrosis. The levels of MIF in lung tissues as well as BAL fluids significantly in
… More
creased in the periods of 5 and 10 days after BLM. Treatment of anti-MIF antibody significantly reduced the mortality at 15 days post-BLM However, the antibody did not affect the historical lung fibrosis score.
2. Role of MIF in monocrotaline(MCT)-induced pulmonary hypertension in rats
We examined the effects of anti-MIF antibody on MCT-induced pulmonary hypertension. Pretreatment with anti-MIF antibody significantly attenuated hypertrophic changes of the right ventricle and the media of the pulmonary artery.
3. Role of MIF in LPS-induced lung injury in MIF-transgenic mice.
To elucidate more detailed functional role of MIF in LPS-induced lung injury, transgenic mice, expressing high levels of MIF, were examined for the neutrophil accumulation in the lungs after LPS administration.
Though we had demonstrated enhanced induction of MIF-mRNA in the lung tissues, we could not find either the increase in the serum MIF levels or increased number of the leukocyte accumulated into the lungs in the LPS-treated transgenic mice.
From these findings, we conclude that MIF play an important role in acute phase of lung injury. Unfortunately, we could not demonstrate enhanced lung injury in LPS treated MIF transgenic mice. One possible reason for this negative finding might be an unknown mechanism that compensates for enhanced MIF production in the transgenic mice. Less
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